This proposal for the continuation of a Specialized Program of Research Excellence (SPORE) in Breast Cancer at the John Hopkins Medical Institutions brings together a highly interactive and productive multidisciplinary program of translational research in breast cancer. The overall goal is reduction in breast cancer incidence, morbidity, and mortality via the focused pursuit of translational research. This renewal application will capitalize on its research momentum and strengths in molecular markers, prevention, and therapy through a portfolio of five integrated and translational research projects. Research Project 1 focuses on identification of molecular markers for progression of ductal carcinoma in situ, building on a successful research program for detecting epigenetic molecular markers. Projects 2, 3, and 4 pursue innovative approaches for breast cancer treatment that have been developed at Johns Hopkins -targeting epigenetic alterations to restore "silenced" gene expression, use of fatty acid synthase inhibitors for breast cancer treatment, and application of combinatorial vaccine approaches to breast cancer. Project 5 explores the development of broccoli sprouts tea as a breast cancer prevention agent. Basic and clinical research investigators in these five research projects are supported by three established and effective core resources, Administration, Human Breast Tissue and Pathology, and Biostatistics. The SPORE also continues a highly productive Developmental Research Program for rapid seed funding of novel ideas at Hopkins and Howard Universities and an outstanding Career Development Program to facilitate career development of individuals with an interest in translational breast cancer research. In aggregate the SPORE will continue to promote translational research by maintaining a breast cancer research culture at Johns Hopkins that transcends academic departments, medical disciplines, and individual research skills and facilitates collaborative research efforts with other SPORE programs.